31 research outputs found
Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist
"Background Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days. Methods Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis. Findings Mean serum IGF-1 concentrations fell by at least 50%: 467 渭g/L (SE 24), 526 渭g/L (29), and 523 渭g/L (40) in patients treated for 6, 12 and 18 months, respectively (p less than 0路001), whereas growth hormone increased by 12路5 渭g/L (2路1), 12路5 渭g/L (3路0), and 14路2 渭g/L (5路7) (p less than 0路001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8路0 渭g/L (2路5) at baseline, rose to 15路2 渭g/L (2路4) on drug, and fell back within 30 days of withdrawal to 8路3 渭g/L (2路7). Antibodies to growth hormone were detected in 27 (16路9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p less than 0路05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11路46 months (0路70) decreased by 0路033 cm3(0路057; p=0路353). Interpretation Pegvisomant is an effective medical treatment for acromegaly.
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Prospective, longitudinal study of cancer predictors and rates in a New York City cohort of 598 patients with acromegaly
This is a prospective, longitudinal study of cancer predictors and cancer rates in a cohort of 598 patients with acromegaly in New York City, USA
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Supplemental Tables 1 and 2 for: Long-term pegvisomant therapy of acromegaly: Effects on bone density, turnover and microstructure using HRpQCT
Supplemental Tables for: Long-term pegvisomant therapy of acromegaly: Effects on bone density, turnover and microstructure using HRpQCT, Journal of the Endocrine Society, 2024
MRI assessment of lean and adipose tissue distribution in female patients with Cushing's disease
OBJECTIVE: Chronic hypercortisolemia due to Cushing鈥檚 Disease (CD) results in abnormal adipose tissue (AT) distribution. Whole-body magnetic resonance imaging (MRI) was used to examine lean and AT distribution in female patients with CD to further understand the role of glucocorticoid excess in the development of abnormal AT distribution and obesity. DESIGN: Cross-sectional and case control study. PATIENTS: 15 females with CD and 12 healthy controls. MEASUREMENTS: Mass of skeletal muscle (SM) and AT in the visceral (VAT), subcutaneous (SAT), and inter-muscular (IMAT) compartments from whole-body MRI and serum levels of insulin, glucose, and leptin were measured. RESULTS: CD patients had leptin values that correlated to total AT (TAT) and SAT (p < 0.05) but not to VAT. CD patients had higher VAT/TAT ratios (p < 0.01) and lower SAT/TAT ratios (p < 0.05) compared to controls. TAT, VAT, and trunk SAT (TrSAT) were greater in CD patients (p < 0.01). SM was less in CD (p < 0.001) but IMAT was not different. CONCLUSIONS: TAT, VAT, trSAT, and the proportion of AT in the visceral depot were greater in CD, though the proportion in the subcutaneous depot was less. SM was less but IMAT was not different. These findings have implications for understanding the role of cortisol in the abnormal AT distribution and metabolic risk seen in patients exposed to chronic excess glucocorticoids
Lower Visceral and Subcutaneous but Higher Intermuscular Adipose Tissue Depots in Patients with Growth Hormone and Insulin-Like Growth Factor I Excess Due to Acromegaly
Context: GH and IGF-I are important regulators of metabolism and body composition. In acromegaly, a state of GH and IGF-I excess, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) distribution